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BFOM Exam 3 > Innate Immunity > Flashcards

Innate Immunity Flashcards

1
Q

Describe the innate defenses that guard against entry of microbes into body tissues

A
  • Biochemical
    • lactic and fatty acids in sweat and sebaceous secretions
    • low pH on skin
    • microbicidal factors in secreted fluids (tears, sweat, stomach acid, etc)
  • Commensal organisms
    • occupy body niches
    • compete for nutrients
    • produce inhibitory substances
  • Mucus
    • produced by membranes lining inner surfaces
    • inhibits adherence of bacteria to epithelial cells
  • Mechanical
    • ciliary action, coughing, sneezing
    • remove microbes caught in mucus
    • flushing actions of urinating, crying, salivating
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2
Q

Distinguish the general characteristics and roles of neutrophils, aka polymorphonuclear leukocytes (PMNs), in innate immunity

A
  • most abundant leukocyte in blood
  • multilobed nucleus
  • number increases drastically during infection and produced by bone marrow
  • ingest microbes in circulation
  • rapidly move into extravascular tissue at site of infection to ingest microbes
  • lifespan of hours to 1-2 days
  • early, short lived responders, but critical
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3
Q

Distinguish the general characteristics and roles of monocytes/macrophages in innate immunity

A 
Monocytes
-produced by bone marrow
-circulate in blood
-ingest microbes in blood and at sites of infection where they can differentiate into macrophages
Macrophages
-resides in tissues throughout the body
-ingest and kill microbes, produce inflammatory cytokines, clear dead cells and initiate tissue repair
-long life span
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4
Q

Describe the general mechanisms by which phagocytes (neutrophils and macrophages) clear microbes

A
  • phagocytosis
  • inflammation
  • enhanced adaptive immunity
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5
Q

Explain the general characteristics and roles of dendritic cells

A
  • produce cytokines

- promote inflammation and adaptive immune response

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6
Q

Explain the general characteristics and roles of mast cells in innate immunity

A
  • contain cytoplasmic granules loaded with proteases (kill bacteria, inactivate toxins) and vasoactive amines (histamines) (vascular permeability)
  • activated by microbes to degranulate and secrete prostaglandins and cytokines
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7
Q

Explain the general characteristics and roles of natural killer (NK) cells in innate immunity

A
  • recognize infected or stressed cells
    • kill targets by degranulating and releasing proteins that trigger apoptosis
    • act in defense against intracellular pathogens (kill infected cells)
  • act cooperatively with macrophages
    • activate IL-12 produced by macrophages
    • secrete interferon-y – activates macrophages
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8
Q

Describe the specific pathways of the complement system

A

Alternative Pathway
- triggered by activation of certain complement proteins on microbial surfaces
Lectin Pathway
-triggered by the binding of mannose-binding lectin to mannose residues on icrbial surface glycoproteins
-innnate immune defense
Classical Pathway
-triggered by antibodies to antigens
-antibody-mediated adaptive immunity
-can also be activated by proteins considered as innate defense proteins

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9
Q

Explain the principal sources and key functions of major cytokines, including tumor necrosis factor (TNF), interleukin(IL)-1, IL-6, IL-10, IL-12, interferon(IFN)-y and type I interferons (IFN-a and IFN-b) in innate immunity

A
  • TNF: hypothalamus = induce fever; liver = acute phase proteins; main cytokine for recruiting neutrophils and monocytes to infection site
  • IL-1: hypothalamus = induce fever; liver = acute phase proteins; main cytokine for recruiting neutrophils and monocytes to infection site
  • IL-6: liver = acute phase proteins
  • IL-10: macrophages, dendritic cells, T cells; inhibition of cytokine and chemokine production, reduced expression of costimulators & class II MHC molecules
  • IL-12: dendritic cells and macrophages; IFN-y production, increased cytotoxic activity
  • IL-y: NK cells, T lymphocytes; activation of macrophages, stimulation of some antibody responses
  • IFN-a/b: plasmacytoid dendritic cells, virus infected cells; bind to receptors of infected cells or neighboring cells; activate signaling pathways that inhibit viral replication
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10
Q

What are specialized lymphocytes?

A

intraepithelial lymphocytes

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11
Q

What are defensins?

A
  • antimicrobials against bacteria, fungi, and viruses
  • small, cationic, cysteine-rich peptides
  • produced by epithelial cells and leukocytes
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12
Q

Explain the concept and function of pathogen-associated molecular patterns (PAMPs) in innate immunity

A
  • structures shared by many classes of microbes
  • not present on human cells
  • recognized by pattern recognition receptors (PRRs)
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13
Q

Explain the concept and function of damage-associated molecular patterns (DAMPs) in innate immunity

A
  • various particles released by damaged or necrotic host cells
  • not released by healthy cells
  • recognized by certain receptors expressed by host cells
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14
Q

Explain the concept and function of pattern recognition receptors (PRRs) in innate immunity

A
  • bind PAMPs and DAMPs
  • expressed by phagocytes, dendritic cells, etc
  • on cell surfaces, endosomes, cytosol
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15
Q

Describe the general features, cellular localization and functions of Toll-like receptors (TLRs)

A
  • family of PRRs
  • each has a ligand-binding domain and cytoplasmic signaling domain
  • specific
  • Cell surface TLR: for microbial proteins, lipids, and polysaccharides (components of extracellular microbes)
  • Endosomal TLR: specific for nucleic acids not found in mammalian cells (intracellular microbes)
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16
Q

What does TLR-9 recognize?

A

CpG (C-G pairs)

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17
Q

What does TLR-3 recognize?

A

dsRNA – we don’t make that

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18
Q

Describe the general features and functions of NOD-like receptors (NLRs), the inflammasome and RIG-like receptors (RLRs)

A

NLR
-NOD1 and NOD2
-activate NFkB
NLRP3
- this + adaptor protein make inflamasome –> activate caspase 1 –> secrete IL-1B –> acute inflammation, fever
RLR – recognize viral RNA –> produce IFN

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19
Q

Compare and contrast the major receptors for innate and adaptive immunity in regard to specificity, expression and self/nonself discrimination

A

Specifity:
-I: specific to PAMPs
-A: specific to antigens, microbial and non-microbial
Expression:
-I: identical receptors on all cells, hundreds
-A: differentiated receptors, 2 types with millions of variations
Self/nonself deiscrimination:
-I: healthy host cells not recognized
-A: based on elimination/inactivation of self-reactive lymphocytes

20
Q

Explain the general features and functions of the acute inflammatory response

A

Rolling:
-microbe enter subepithelial tissue
-microbe activates macrophages & dendritic cells
-production of TNF and IL-1 which stimulate expression of E-selectin by vascular endothelium
-blood leukocytes begin to bind thru selectin-ligand to E-selectin
Integrin Activation by Chemokines
-production of chemokines by activated innate defense cells and endothelial cells
-chemokines stimulate blood leukocytes
-increased affinity of leukocyte integrins
Stable Adhesion
-TNF & IL-1 stimulate expression of integrin ligands by endothelium
-stable binding of integrins to integrin ligands
-arrest of rolling leukocytes on endothelium
-re-organization of leukocyte cytoskeleton
Migration Through Epithelium
-chemokines and other chemoattractants stimulate leukocyte motility
-leukocytes migrate between endothelial cells

21
Q

Examples of NLRs

A

NOD-1 & NOD-2
- activate NF-kB
-specific for bacterial peptidoglycan
NLRP-3
-specific for microbial products and DAMPs
-interacts with adaptor protein and caspase-1 to form inflammasome
-caspase-1 generates active IL-1B –> acute inflammation and fever

22
Q

Examples of RLR

A 
Cytosolic RNA sensors
-recognize viral RNA
-induce production of type I interferons
Cytosolic DNA sensors
-recognize microbial dsDNA
-induce production of type I IFN
Lectin receptors
-cell surface; recognize carbohydrates
-promote phagocytosis and inflammatory responses
23
Q

What are the phagolysosome killing mechanisms?

A
  • phagocyte oxidase –>reactive oxygen species(ROS)
  • inducible nitric oxide synthase (iNOS) –> nitric oxide (NO)
  • lysosomal proteases
24
Q

What happens when reactive oxygen species (ROS) and nitric oxide (NO) are released by phagocytes?

A
  • kill extracellular microbes (good)

- damage tissues (bad)

25
Q

Difference between neutrophil and macrophage: origin

A

N: bone marrow
M: bone marrow in inflammatory reactions and some reside in tissues (stem cells in yolk salc of fetal liver)

26
Q

Difference between neutrophil and macrophage: life span in tissues

A

N: 1-2 days
M: inflammatory - days or weeks; tissue residents - years

27
Q

Difference between neutrophil and macrophage: responses to activating stimuli

A

N: rapid, short-lived enzymatic activity
M: more prolonged, slower, dependent on new gene transcription

28
Q

Difference between neutrophil and macrophage: phagocytosis

A

N: rapid ingestion
M: prolonged ativity to ingest microbes, apoptotic cells, tissue debris, foreign material

29
Q

Difference between neutrophil and macrophage: ROS

A

N: rapidly induced by assembly of phagocyte oxidase (respiratory burst)
M: less prominent

30
Q

Difference between neutrophil and macrophage: NO

A

N: low levels - none
M: induced following transcriptional activation of iNOS

31
Q

Difference between neutrophil and macrophage: degranulation

A

N: major response induced by cytoskeletal rearrangement
M: not prominent

32
Q

Difference between neutrophil and macrophage: cytokine production

A

N: low levels per cell
M: major functional ability – requires transcriptional activation of cytokine genes

33
Q

Difference between neutrophil and macrophage: Extracellular Traps

A

(nucleic acids spilling out of the cell and keeps microbes from leaving (pus))
N: rapidly induced
M: little

34
Q

Difference between neutrophil and macrophage: secretion of lysosomal enzymes

A

N: prominent
M: less

35
Q

What are mucosal associated variant T (MAIT) cells?

A
  • in mucosal tissue, esp. liver

- innate defense against intestinal bacteria

36
Q

What are gamma delta T cells?

A
  • intraepithelial cell (IEL)

- recognize microbial lipids

37
Q

What are NK-T cells?

A
  • in epithelia and lymphoid organs

- recognize microbial lipids

38
Q

What are B-1 cells?

A
  • in peritoneal cavity and mucosal tissues
  • produce antibodies in response to microbes and microbial toxins in gut
  • produce “natural antibodies”
39
Q

What are marginal zone B cells?

A
  • edge of lymphoid follicles of spleen

- critical role in antibody responses to blood-borne polysaccharide-rich bacteria

40
Q

Describe the general features and functions of the complement system in innate immunity

A
  • many complement proteins act as proteases
  • Plasma protein C3: central component; cleaved early in cascade (C3a and C3b)
  • C3b acts as an opsonin and coats microbes –> facilitates phagocytosis
  • C3a and C5a act as chemoattractants…promote leukoxyte recruitement (inflammation)
  • microbial attack complex (MAC): microbial lysis
41
Q

Describe the general function of the acute phase proteins in innate immunity and examples

A
  • circulating levels of plasma proteins made by the liver rapidly increase after infection
  • -mannose-binding lectin (MBL): binds mannose on microbial carbohydrates, aactivates complement cascade via lectin pathway, act as an opsonin (lectic receptor on phagocytes)
  • -C-reactive protein (CRP): binds phosphorylcholine on microbes, act as opsonin (CRP receptor on macrophages), activates complement via classical pathway, common blood test to assess infection/inflammation
42
Q

What are cytokines?

A
  • soluble proteins that mediate immune and inflammatory reactions
  • critical mediator of communication between the immune system and itself and with other cells
  • typically secreted in small amounts and bind to high affinity receptors
  • most act in autocrine or paracrine fashion, but can do endocrine signalingg in large quantities
43
Q

What are interleukins?

A

molecularly defined cytokines

44
Q

What are chemokines?

A
  • family of structurally low -molecular weight cytokines
  • stimulate leukocyte chemotaxis
  • regulate leukocyte migration from blood into tissues by activating leukocyte integrins
  • mediate spacial organization of immune cells with lymphoid organs
45
Q

What happens when there are high levels of TNF?

A
  • thrombus formation on endothelium

- lowered myocardial contractility + increased vasodilation & leakiness = lowered BP

46
Q

What is sepsis?

A
  • disseminated bacterial infection

- high levels of TNF, low BP, disseminated intravascular coagulation (DIC)

BFOM Exam 3 (19 decks)

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